Structure-based redesign of proteins for minimal T-cell epitope content

Copyright © 2013 Wiley Periodicals, Inc.

Bibliographische Detailangaben
Veröffentlicht in:Journal of computational chemistry. - 1984. - 34(2013), 10 vom: 05. Apr., Seite 879-91
1. Verfasser: Choi, Yoonjoo (VerfasserIn)
Weitere Verfasser: Griswold, Karl E, Bailey-Kellogg, Chris
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2013
Zugriff auf das übergeordnete Werk:Journal of computational chemistry
Schlagworte:Journal Article Research Support, N.I.H., Extramural Epitopes, T-Lymphocyte Proteins
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520 |a The protein universe displays a wealth of therapeutically relevant activities, but T-cell driven immune responses to non-"self" biological agents present a major impediment to harnessing the full diversity of these molecular functions. Mutagenic T-cell epitope deletion seeks to mitigate the immune response, but can typically address only a small number of epitopes. Here, we pursue a "bottom-up" approach that redesigns an entire protein to remain native-like but contain few if any immunogenic epitopes. We do so by extending the Rosetta flexible-backbone protein design software with an epitope scoring mechanism and appropriate constraints. The method is benchmarked with a diverse panel of proteins and applied to three targets of therapeutic interest. We show that the deimmunized designs indeed have minimal predicted epitope content and are native-like in terms of various quality measures, and moreover that they display levels of native sequence recovery comparable to those of non-deimmunized designs 
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700 1 |a Griswold, Karl E  |e verfasserin  |4 aut 
700 1 |a Bailey-Kellogg, Chris  |e verfasserin  |4 aut 
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